scholarly journals Ets1 Promotes the Differentiation of Post-Selected iNKT Cells through Regulation of the Expression of Vα14Jα18 T Cell Receptor and PLZF

2021 ◽  
Vol 22 (22) ◽  
pp. 12199
Author(s):  
Ya-Ting Chuang ◽  
Wan-Chu Chuang ◽  
Chih-Chun Liu ◽  
Chia-Wei Liu ◽  
Yu-Wen Huang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Target Genes ◽  
Cell Receptor ◽  
Mechanisms Of Action ◽  
Inkt Cells ◽  
Genome Wide ◽  
Invariant Natural Killer ◽  
Multiple Stages ◽  
Molecular Picture

The transcription factor Ets1 is essential for the development/differentiation of invariant Natural Killer T (iNKT) cells at multiple stages. However, its mechanisms of action and target genes in iNKT cells are still elusive. Here, we show that Ets1 is required for the optimal expression of the Vα14Jα18 T cell receptor (TCR) in post-selected thymic iNKT cells and their immediate differentiation. Ets1 is also critical for maintaining the peripheral homeostasis of iNKT cells, which is a role independent of the expression of the Vα14Jα18 TCR. Genome-wide transcriptomic analyses of post-selected iNKT cells further reveal that Ets1 controls leukocytes activation, proliferation differentiation, and leukocyte-mediated immunity. In addition, Ets1 regulates the expression of ICOS and PLZF in iNKT cells. More importantly, restoring the expression of PLZF and the Vα14Jα18 TCR partially rescues the differentiation of iNKT cells in the absence of Ets1. Taken together, our results establish a detailed molecular picture of how Ets1 regulates the stepwise differentiation of iNKT cells.

A divergent approach to the synthesis of iGb3 sugar and lipid analogues via a lactosyl 2-azido-sphingosine intermediate

2014 ◽  
Vol 12 (17) ◽  
pp. 2729-2736 ◽  
Author(s):  
Janice M. H. Cheng ◽  
Emma M. Dangerfield ◽  
Mattie S. M. Timmer ◽  
Bridget L. Stocker
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Inkt Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T

Isoglobotrihexosylceramide (iGb3, 1) is an immunomodulatory glycolipid that binds to CD1d and is presented to the T-cell receptor (TCR) of invariant natural killer T (iNKT) cells.

scholarly journals Analyzing the Mycobacterium tuberculosis immune response by T-cell receptor clustering with GLIPH2 and genome-wide antigen screening

2020 ◽  
Vol 38 (10) ◽  
pp. 1194-1202 ◽  
Author(s):  
Huang Huang ◽  
Chunlin Wang ◽  
Florian Rubelt ◽  
Thomas J. Scriba ◽  
Mark M. Davis
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Clustering ◽  
Genome Wide

scholarly journals Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor

2005 ◽  
Vol 6 (8) ◽  
pp. 810-818 ◽  
Author(s):  
Dirk M Zajonc ◽  
Carlos Cantu ◽  
Jochen Mattner ◽  
Dapeng Zhou ◽  
Paul B Savage ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Structure And Function ◽  
Natural Killer T Cell ◽  
Potent Agonist ◽  
And Function ◽  
Invariant Natural Killer ◽  
Killer T Cell

scholarly journals 9-cis retinoic acid inhibition of activation-induced apoptosis is mediated via regulation of fas ligand and requires retinoic acid receptor and retinoid X receptor activation.

1995 ◽  
Vol 15 (10) ◽  
pp. 5576-5585 ◽  
Author(s):  
R P Bissonnette ◽  
T Brunner ◽  
S B Lazarchik ◽  
N J Yoo ◽  
M F Boehm ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
T Cell ◽  
T Cell Receptor ◽  
Target Genes ◽  
Fas Ligand ◽  
Apoptotic Cell ◽  
Cell Receptor ◽  
Receptor Activation ◽  
Retinoid Receptor ◽  
Induced Apoptosis

T-cell hybridomas, thymocytes, and T cells can be induced to undergo apoptotic cell death by activation through the T-cell receptor. This process requires macromolecular synthesis and thus gene expression, and it has been shown to be influenced by factors regulating transcription. Recently, activation, T-cell hybridomas rapidly express the Fas/CD95 receptor and its ligand, Fas ligand (FasL), which interact to transduce the death signal in the activated cell. Retinoids, the active metabolites of vitamin A, modulate expression of specific target genes by binding to two classes of intracellular receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs). They are potent modulators of apoptosis in a number of experimental models, and they have been shown to inhibit activation-induced apoptosis in T-cell hybridomas and thymocytes. Particularly effective is the prototypic pan-agonist 9-cis retinoic acid (9-cis RA), which has high affinity for both RARs and RXRs. We report here that 9-cis RA inhibits T-cell receptor-mediated apoptosis in T-cell hybridomas by blocking the expression of Fas ligand following activation. This inhibition appears to be at the level of FasL mRNA, with the subsequent failure to express cell surface FasL. RAR-selective (TTNPB) or RXR-selective (LG100268) ligands alone were considerably less potent than RAR-RXR pan-agonists. However, the addition of both RAR- and RXR-selective ligands was as effective as the addition of 9-cis RA alone. The demonstrates that the inhibitory effect requires the ligand-mediated activation of both retinoid receptor signaling pathways.

scholarly journals The Total Synthesis of Proposed Immunoactive Glycolipids from S. Pneumoniae and a Re-evaluation of Their Immunological Activity

2021 ◽  
Author(s):  
Seyed Iraj Sadraei ◽  
Greg Yousif ◽  
S. Maryamdokht Taimoory ◽  
Emmanuel Igbokwe ◽  
Samaneh Mehri ◽  
...  
Keyword(s):  
T Cell ◽  
Total Synthesis ◽  
T Cell Receptor ◽  
Mammalian Species ◽  
White Blood Cells ◽  
Computational Modelling ◽  
Cell Receptor ◽  
Binary Complex ◽  
Inkt Cells ◽  
High Degree

<p>Invariant natural killer T cells (iNKT), a subclass of white blood cells, are responsible for the production of pro-inflammatory cytokines which induce a systemic immune response. They are distinctive in having an invariant T-cell receptor that recognizes glycolipid antigens presented by the class I major histocompatibility complex-related protein CD1d, which is conserved across multiple mammalian species in a class of proteins well-renowned for their high degree of polymorphism. This receptor’s first identified antigen is the potent KRN7000, a glycosphingolipid isolated from bacteria that were found on a Japanese marine sponge. The corresponding terrestrial antigen remained unidentified until quite recently, when diacylglycerol-containing glycolipids, reported to activate iNKT cells, were isolated from <i>Streptococcus pneumoniae</i>. We report the total synthesis and immunological re-evaluation of these two glycolipids. The compounds are unable to activate iNKT cells. Computational modelling shows that these ligands, while being capable of interacting with the CD1d receptor, create a different surface for the binary complex that makes formation of the ternary complex with the iNKT T-cell receptor difficult. Together these results suggest that the reported activity might have been due to an impurity in the original isolated sample, and highlights the importance of taking care when reporting biological activity from isolated natural products.<b></b></p>

scholarly journals Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation

2018 ◽  
Vol 115 (17) ◽  
pp. E4051-E4060 ◽  
Author(s):  
Wanjing Shang ◽  
Yong Jiang ◽  
Michael Boettcher ◽  
Kang Ding ◽  
Marianne Mollenauer ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
T Cell Activation ◽  
Cell Activation ◽  
Active Form ◽  
Cell Receptor ◽  
Small Gtpase ◽  
Genome Wide ◽  
A Genome ◽  
Crispr Screen

Despite decades of research, mechanisms controlling T cell activation remain only partially understood, which hampers T cell-based immune cancer therapies. Here, we performed a genome-wide CRISPR screen to search for genes that regulate T cell activation. Our screen confirmed many of the known regulators in proximal T cell receptor signaling and, importantly, also uncovered a previously uncharacterized regulator, FAM49B (family with sequence similarity 49 member B). FAM49B deficiency led to hyperactivation of Jurkat T cells following T cell receptor stimulation, as indicated by enhancement of CD69 induction, PAK phosphorylation, and actin assembly. FAM49B directly interacted with the active form of the small GTPase Rac, and genetic disruption of the FAM49B–Rac interaction compromised FAM49B function. Thus, FAM49B inhibits T cell activation by repressing Rac activity and modulating cytoskeleton reorganization.

scholarly journals Structural Basis for the Recognition of C20:2-αGalCer by the Invariant Natural Killer T Cell Receptor-like Antibody L363

2011 ◽  
Vol 287 (2) ◽  
pp. 1269-1278 ◽  
Author(s):  
Esther Dawen Yu ◽  
Enrico Girardi ◽  
Jing Wang ◽  
Thien-Thi Mac ◽  
Karl O. A. Yu ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Structural Basis ◽  
Natural Killer T Cell ◽  
Invariant Natural Killer ◽  
Killer T Cell ◽  
Natural Killer T

scholarly journals Binding Strength and Dynamics of Invariant Natural Killer Cell T Cell Receptor/CD1d-Glycosphingolipid Interaction on Living Cells by Single Molecule Force Spectroscopy

2011 ◽  
Vol 286 (18) ◽  
pp. 15973-15979 ◽  
Author(s):  
Bianca L. Bozna ◽  
Paolo Polzella ◽  
Christian Rankl ◽  
Rong Zhu ◽  
Mariolina Salio ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
T Cell Receptor ◽  
Single Molecule ◽  
Killer Cell ◽  
Force Spectroscopy ◽  
Cell Receptor ◽  
Living Cells ◽  
Single Molecule Force Spectroscopy ◽  
Invariant Natural Killer

Invariant natural killer T (iNKT) cells are a population of T lymphocytes that play an important role in regulating immunity to infection and tumors by recognizing endogenous and exogenous CD1d-bound lipid molecules. Using soluble iNKT T cell receptor (TCR) molecules, we applied single molecule force spectroscopy for the investigation of the iNKT TCR affinity for human CD1d molecules loaded with glycolipids differing in the length of the phytosphingosine chain using either recombinant CD1d molecules or lipid-pulsed THP1 cells. In both settings, the dissociation of the iNKT TCR from human CD1d molecules loaded with the lipid containing the longer phytosphingosine chain required higher unbinding forces compared with the shorter phytosphingosine lipid. Our findings are discussed in the context of previous results obtained by surface plasmon resonance measurements. We present new insights into the energy landscape and the kinetic rate constants of the iNKT TCR/human CD1d-glycosphingolipid interaction and emphasize the unique potential of single molecule force spectroscopy on living cells.

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